Amino Acid Supplementation in Recovery From Severe Burns (ExAA)

Amino Acid Benefits in Pediatric Burn Patients Who Participate in Exercise.

Exercise during recovery is now Standard of Care at Shriners Hospital for Children Galveston, since positive effects of exercise training were found on lean body mass and recovery after burns. Essential amino acids (EAA) effective in healthy individuals.Thus, EAA supplementation in children recovering from burns, may potentially augment the effects of exercise by increase muscle mass, improve muscle fat oxidation, reduce tissue fat, and possibly improve insulin resistance.

Study Overview

• Status: Completed
• Conditions: Burn Injury
• Intervention / Treatment: Dietary supplement: EAA Supplementation + Exercise Training; Dietary supplement: Placebo + Exercise Training

Detailed Description

Severe burns result in persistent and extensive fat deposition in liver and muscle tissue. This may be related to the prolonged insulin resistance observed following burn. In this study the investigators will test the hypothesis that essential amino acids act in synergy with exercise to improve liver steatosis and muscle lipid metabolism, and thus also affect insulin sensitivity. Children with burns will participate in six weeks of exercise training with/without amino acid supplementation. Before and after the intervention, measurements will be done to determine muscle and liver fat content, muscle fat and protein metabolism, and insulin sensitivity.

We will prospectively enroll 40 children with ≥30% of their total body surface area (TBSA) burned. The age range will be 7-17 years. Children will be recruited from Shriners Hospitals for Children (SHC)-Galveston. Burned children will be randomized to undergo an exercise program in combination with daily intake of EAA (n=20) or a placebo drink (n=20). The exercise program and daily intake of AA will begin within the first week of discharge from the burn ICU (approximately 1-3 months post burn, when the patient's wounds are 95% healed). The definition of 95% healed is 7 days after the final autografting procedure. We anticipate enrolling 10 children per year for 4 years. Only children meeting the inclusion and exclusion criteria specified in the Human Subjects Section will be enrolled.

Nutritional Supplement: The nutritional supplement will be administered at a dose of 0.18 g/kg body weight of amino acids two times per day with the following composition: 3% histidine, 9% isoleucine, 36% leucine, 17% lysine, 4% methionine, 5% phenylalanine, 10% threonine, 7% valine, and 10% arginine. The dose and choice of amino acids is based on our preliminary data. Each dose is about 0.03 g/kg body weight higher than what has been shown effective in adults, as children have higher protein needs. We have shown that only EAA are needed to affect muscle protein synthesis and lean mass. Thus the amount given (g or kcal) can be restricted. As in our preliminary studies, we will include arginine in the EAA mixture, since arginine may have unique anabolic effects (55; 86). Placebo will consist of a mixture of inert components (sucralose and other pharmaceutical excipients). The supplement will be taken in two daily doses in the form of drinks (total daily dose of i.e., 0.30 g/kg body weight total per day), and intake recorded in a diary. The first dose will be taken between breakfast and lunch, and the second between lunch and dinner. For the children exercising before lunch, the first dose of EAA will be ingested immediately after exercise. Correspondingly, for children exercising after lunch, the second EAA dose of the day will be ingested immediately after exercise. If the child forgets to take one of the drinks during the day, he/she may take the second one between dinner and bedtime. During the weekends, parents/caregivers are instructed to take the dosage around the same time.

Data Analysis and Interpretation. To determine effects of amino acids on fat and muscle lipid stores, changes from pre- to post intervention in the two groups will be compared using ANCOVA. From the preliminary data, we expect that amino acids will decrease liver and plasma lipids.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Texas
    • Galveston, Texas, United States, 77550
      • Shriners Hospitals for Children

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 7 years to 17 years (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or female
2. 7-17 years old
3. Body weight >20 kg (based on blood requirements)
4. ≥30% Total Body Surface Area (TBSA)
5. Wounds 95% healed

Exclusion Criteria:

1. Respiratory insufficiency
2. Multiple fractures
3. History of Cancer in the last 5 years
4. Diabetes Mellitus
5. Bilirubin > 3 mg/dl
6. Associated head injuries requiring specific therapy
7. Associated injuries to chest or abdomen requiring surgery
8. Serum creatinine > 3 mg/dl after fluid resuscitation
9. Receipt of any experimental drug other than the ones supplied within two months of this study
10. Any metal in body including rods, cardiac defibrillator, pacemakers, etc
11. Orthopedic casting which would prevent placement of patient in MRI machine
12. Hepatitis
13. Abnormal EKG
14. Electrical burns
15. Patients unable to lie still without heavy sedation will be excluded from MRI portion.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: EAA Supplementation + Exercise Training; Drink an amino acid supplementation during exercise training.	Dietary supplement: EAA Supplementation + Exercise Training; Amino acids in drinks between meals for exercise training period.
PLACEBO_COMPARATOR: Placebo + Exercise Training; Drink a placebo supplementation during exercise training.	Dietary supplement: Placebo + Exercise Training; Placebo supplementation as drinks in between meals for exercise training period.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Lean Muscle Mass	Is the total weight of your body minus all the weight due to your fat mass. It is measured in kilograms by dual X-ray absorptiometry scan.	It is the change in time, from baseline until post exercise. Baseline is within the first week of discharge from the burn ICU, approximately 1-3 months post burn. Exercise training is 6-12 weeks.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
whole body lipolysis rate	A euglycemic-hyperinsulinemic clamp is performed over the last 2hr of the 4-hr isotope infusion. It is measured in μmol/kg body weight/min	It is the change in time, from baseline until post exercise. Baseline is within the first week of discharge from the burn ICU, approximately 1-3 months post burn. Exercise training is 6-12 weeks.
Hepatic glucose release rate and whole body glucose uptake rate	A primed, constant (0.44 μmol/kg/min) infusion of [6,6-2H2]-glucose is used for glucose kinetics. A euglycemic-hyperinsulinemic clamp is performed over the last 2h of the 4-hr isotope infusion.It is measured in μmol/kg body weight/min.	It is the change in time, from baseline until post exercise. Baseline is within the first week of discharge from the burn ICU, approximately 1-3 months post burn. Exercise training is 6-12 weeks.

Collaborators and Investigators

• Sponsor: The University of Texas Medical Branch, Galveston
• Collaborators: Shriners Hospitals for Children
• Investigators: Principal Investigator: Oscar E Suman, PhD, UTMB, Shriners Hospitals for Children

Study record dates

Study Major Dates

• Study Start: May 1, 2012
• Primary Completion (ACTUAL): December 5, 2016
• Study Completion (ACTUAL): December 5, 2017

Study Registration Dates

• First Submitted: May 30, 2012
• First Submitted That Met QC Criteria: June 11, 2012
• First Posted (ESTIMATE): June 13, 2012

Study Record Updates

• Last Update Posted (ACTUAL): December 11, 2018
• Last Update Submitted That Met QC Criteria: December 7, 2018
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Keywords: insulin sensitivity; nutrition; children; lipid metabolism; amino acids; burn injury
• Additional Relevant MeSH Terms: Wounds and Injuries; Burns
• Other Study ID Numbers: 12-048

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No